The purpose of this study was to determine the progress of the immunization program for Contagious Diseases in the City Schools of Dallas, Texas, over a period of ten years, dating from September 1928, to September 1938. An endeavor was made to determine how the Health Works Program of the Dallas Public Schools developed, and the protection it gave the public children.

Background: Although immunisation services are provided free at all public health facilities in South Africa, immunisation coverage remains variable and disease outbreaks still occur. The coverage rate in the Overberg district is recorded as 75.8%, below the national target of 90% (Western Cape Government Provincial Treasury 2013:2). The researcher wanted to understand what the barriers to accessing immunisation services were and how this might relate to other primary health care services. Methods: The researcher visited 22 households and interviewed nine mothers who had brought their children to Zwelihle Clinic to be immunised and nine community health workers servicing the Zwelihle community in the Overberg district, Western Cape Province. Findings: A key finding is that the data does not reflect the actual situation – children in the community either are immunised at other facilities or have left the catchment area, hence strong relationships between the facility and the community and an electronic patient tracking system become important. Findings impacting access to services include the attitude of administrative staff, waiting times and the impact of migratory communities. Recommendations are made to improve the quality of data, provide training to administrative staff, improve patient education, reduce waiting times and improve the relationship between the clinic and the community in order to better track patient migration / Health Studies / M.A. (Public Health)

Skin is the largest immune organ and an ideal site to administer vaccines. However, by nature, skin is not permeable to antigens, which are macromolecules. The major hurdle in skin permeation is the outermost stratum corneum layer. Microneedles have proven feasible to create micron-sized channels in the epidermis of the skin, through which protein and plasmid DNA antigens can penetrate into the viable skin epidermis and dermis. However, the immune responses induced by microneedle-mediated transcutaneous immunization with protein or plasmid DNA alone are generally weak, and a vaccine adjuvant is often required to induce strong immune responses. Data from numerous previous studies have shown that nanoparticles as a vaccine carrier can significantly enhance the immunogenicity of antigens, but the feasibility of utilizing nanoparticles as a vaccine carrier to enhance the immune responses induced by microneedle-mediated transcutaneous immunization has rarely been studied. In this dissertation, using protein antigen (OVA) chemically conjugated onto the surface of solid-lipid nanoparticles and plasmid DNA (pCMV-beta, pVax/opt-BoNT/C-Hc50, and pCI-neo-sOVA) physically coated on the surface of cationic polymeric nanoparticles, we showed that the immune responses induced by microneedle-mediated transcutaneous immunization with protein antigens or plasmid DNA vaccines are significantly enhanced by delivering the proteins and plasmid DNA with nanoparticles. Importantly, microneedle-mediated transcutaneous immunization with proteins or plasmid DNA induces not only systemic immune responses, but also mucosal immune responses. In addition, it is generally believed that microneedles are safe. However, it remained unclear whether the micropores created by microneedles on the skin will also facilitate the permeation of microbes such as bacteria into the skin. In this dissertation, we also designed an unique ex vivo model to evaluate the permeation of live bacteria through mouse skin pretreated with microneedles. The results demonstrated that the risk of potential bacterial infection associated with microneedle treatment is not greater than that associated with a hypodermic needle injection. / text

This thesis consists of five papers. In the first two papers we consider a general approach to cash flow valuation, focusing on dynamic properties of the value of a stream of cash flows. The third paper discusses immunization theory, where old results are shown to hold in general deterministic models, but often fail to be true in stochastic models. In the fourth paper we comment on the connection between arbitrage opportunities and an immunized position. Finally, in the last paper we study coherent and convex measure of risk applied to portfolio optimization and insurance.

Purpose: The primary objective of this study was to estimate the prevalence of vaccination and HBV infection status of adults and to evaluate the trend in self reported vaccination and seroprevalence for Hepatitis B for this population. Additionally, this study sought to assess the association between vaccination rates, seroprevalence (HBsAg, anti-HBc, and anti-HBs), demographic (age, gender, location of birth, race/ethnicity), and socioeconomic (annual household income, education level, insurance coverage and access to care, marital status) characteristics. Methods: Eight years, 1999-2006, of the National Health and Nutrition Examination Survey (NHANES) data were used. NHANES participants aged 20-59 years who contributed data via the household interview and laboratory component were eligible for this study. Two sources of vaccination status were available. The vaccination status was identified through self-report. Those who answered yes to “less than three doses” and “at least three doses” were classified as vaccinated. Vaccination status was also verified through serologic markers. All analyses were weighted to consider the complex weighting scheme and adjusted to the 2000 US census population. Vaccination rates were calculated for both low and high risk populations. 95% confidence intervals (95% CI) of each estimate were also calculated. The association between potential predictors of vaccination (demographic variables, socioeconomic status, high risk, and health care access and utilization variables) and vaccination status was assessed using bivariate analysis. We used logistic regression model to obtain odds ratios and their 95% confidence intervals for the association between predictor variables and vaccination status after adjusting for all potential confounding factors. Results: Vaccinated adults were more likely to be female, younger (20-29), Non-Hispanic white, married, born in the United States, have some education beyond high school, have a household income greater than $20000, health insurance coverage, a source of usual medical care, report a health status of good or higher, be non-smokers, and have no history of alcohol abuse. High risk adults comprised about 16% of adults who had received at least one dose of the Hepatitis B vaccine. Unvaccinated adults were more likely to be male, over the age of 40, Non-Hispanic white, born in the United States, married, have some education beyond high school, have a household income greater than $20,000, live in a household of 6 or fewer people, have health insurance coverage, and a source of usual care. When comparing the self reported vaccination status with serologic status, almost half of the adults who reported receiving all three doses of the vaccine tested negative for immunity. For all adults the prevalence increased from 23.4% to 39.1%. Compared to adults in 1999-2000, adults were twice as likely to report vaccination in 2005-2006 (OR=2.1 95% CI [1.77, 2.49]). Conclusions: Although, hepatitis B vaccination rates are rising, only 32% of high risk adults are vaccinated. The rise in vaccination rates in young adults is mostly related to childhood immunization strategies and not strategies aimed at adults. Older males, those with less than high school education, without health insurance coverage and a source of usual care were least likely to be vaccinated. More targeted interventions are needed to educate and vaccinate the adult population and to create a means for identifying those at risk and those already vaccinated.

Estudo observacional transversal que teve como objetivos caracterizar os pacientes com diabetes mellitus segundo as variáveis demográficas e clínicas; estimar a prevalência de infecção pelo vírus da hepatite B e C e a cobertura vacinal contra hepatite B em pacientes com diabetes mellitus e identificar potenciais fatores de risco relacionados. A amostra de conveniência foi constituída de 255 pacientes com diabetes mellitus que compareceram à consulta médica nos ambulatórios de Endocrinologia e de Clínica Médica Integrado de Unidade Distrital de Saúde de Ribeirão Preto-SP, no período de julho a dezembro de 2014. As variáveis demográficas selecionadas foram sexo, idade e escolaridade e, as clínicas o uso de insulina, monitoramento da glicemia capilar, história de intervenções médicas, cirúrgicas, diagnósticas e terapêuticas e situações e comportamentos de risco para hepatite B e C. Os marcadores sorológicos investigados foram HBsAg, Anti-HBc IgG, Anti-HBc IgM, Anti-HBs e Anti-HCV. Considerou-se vacinação completa três ou mais doses da vacina contra hepatite B registrada. Para a coleta de dados utilizou-se um questionário, consulta ao registro de vacinação no Sistema Informatizado de Gestão em Saúde da Secretaria Municipal de Saúde e coleta de sangue venoso. Os dados foram apresentados por meio de estatística descritiva. A análise univariada das possíveis associações entre as variáveis demográficas e clínicas e os desfechos infecção pelo vírus da hepatite B e C e cobertura vacinal contra hepatite B, foi determinada pelos testes de Qui-quadrado corrigido por Pearson ou Teste exato de Fisher bicaudal e Wilcoxon para amostras não pareadas. Para a análise multivariada, foi construído um modelo de regressão logística onde foram incluídas as variáveis que exibiram p<0,2 na análise univariada. Valores de \'p\' inferiores a 5% foram considerados significativos. Os resultados mostraram que 16,8% dos pacientes apresentaram marcador Anti-HBc total reagente, 8,2% Anti-HBs isolado e 75% foram não reagentes para todos os marcadores de hepatite B. Nenhum caso de HBsAg reagente foi encontrado na amostra estudada. Quanto à infecção pelo vírus da hepatite C, 3,3% dos pacientes apresentaram marcador anti-HCV reagente. A prevalência de infecção pelo vírus da hepatite B (Anti-HBc reagente) em pacientes com diabetes mellitus foi de 16,8%, superior à nacional e mostrou-se diretamente associado ao tempo da doença. A prevalência de infecção pelo vírus da hepatite C (Anti-HCV reagente) foi de 3,3%, superior à nacional, mas não teve associação com as variáveis demográficas e clínicas investigadas. A cobertura vacinal contra hepatite B mostrou-se baixa (15%) em pacientes com diabetes mellitus evidenciando a sua vulnerabilidade a essa doença grave e potencialmente fatal. Maior escolaridade e o trabalho na área da saúde foram associados à melhor cobertura vacinal. Estes resultados fornecem subsídios importantes para a avaliação da prática clínica dos enfermeiros na atenção primaria à saúde para a prestação de cuidados relacionados à cobertura vacinal a pessoas com diabetes mellitus. Assim, esforços devem ser empenhados pelos profissionais e serviços de saúde para enfrentar o desafio de prover ampla cobertura vacinal a essa população, garantindo a prevenção da infecção pelo vírus da hepatite B e C / A cross-sectional observational study aimed at characterizing patients with diabetes mellitus according to demographic and clinical variables; to estimate the prevalence of hepatitis B and C virus infection and vaccine coverage in patients with diabetes mellitus and to identify potential related risk factors. The convenience sample consisted of 255 patients with diabetes mellitus who attended the medical consultation in the outpatient clinics of Endocrinology and Integrated Medical Clinic of the District Health Unit of Ribeirão Preto-SP, from July to December 2014. The selected demographic variables the use of insulin, capillary blood glucose monitoring, history of medical, surgical, diagnostic and therapeutic interventions and risky situations and behaviors for hepatitis B and C. The serological markers investigated were HBsAg, Anti -HBc IgG, Anti-HBc IgM, Anti-HBs and Anti-HCV. Three or more doses of the registered hepatitis B vaccine were considered complete vaccination. To collect data, a questionnaire was used, consulting the vaccination record of the Health Management Computerized System of Health of the Municipal Health Department and venous blood collection. The data were presented by means of descriptive statistics. Univariate analysis of possible associations between demographic and clinical variables and outcomes of hepatitis B and C virus infection and vaccine coverage against hepatitis B was determined by the Pearson-corrected chi-square test or Wilcoxon\'s exact Fisher\'s test for Unpaired samples. For the multivariate analysis, a logistic regression model was constructed in which variables that exhibited p <0.2 were included in the univariate analysis. Values of \'p\' below 5% were considered significant. The results showed that 16.8% of the patients presented total anti-HBc marker reagent, 8.2% Anti-HBs alone and 75% were non-reactive for all hepatitis B markers. No case of HBsAg reagent was found in the sample studied. Regarding hepatitis C virus infection, 3.3% of the patients presented anti-HCV marker reagent. The prevalence of hepatitis B virus (Anti-HBc reagent) in patients with diabetes mellitus was 16.8% higher than the national level and was directly associated with the time of diabetes mellitus. The prevalence of hepatitis C virus infection (Anti-HCV reagent) was 3.3%, higher than the national level, but had no association with the demographic and clinical variables investigated. Hepatitis B vaccination coverage was shown to be low (15%) in patients with diabetes mellitus evidencing their vulnerability to this serious and potentially fatal disease. Higher schooling and work in the health area were associated with better vaccine coverage. These results provide important insights for the evaluation of nurses\' clinical practice in primary health care for care related to vaccination coverage for people with diabetes mellitus. Thus, efforts must be made by health professionals and services to meet the challenge of providing ample vaccination coverage to this population, ensuring the prevention of hepatitis B and C virus infection

Alguns estudos têm proposto que os acidente ofídicos em crianças estão associados a maior gravidade e ao maior risco de desenvolvimento de complicações comparados aos acidentes em adultos. Este estudo retrospectivo descreve as características de acidentes causados por serpentes do gênero Bothrops admitidos no Hospital Vital Brazil/Instituto Butantan/SP (HVB/IB) e compara a gravidade, e necessidade de soroterapia antiveneno e o risco para o desenvolvimento de complicações entre crianças (menores de 13 anos) e adultos. Trata-se de uma coorte histórica que utilizou dados de prontuários do arquivo do HVB/IB de dezembro de 1999 a junho de 2003. Foram incluídos no estudo pacientes que trouxeram a serpente ou apresentavam manifestações clínicas ou laboratoriais compatíveis com envenenamento botrópico. Não foi observada diferença estatisticamente significante na freqüência da gravidade dos envenenamentos, no número de ampolas administradas e na freqüência de complicações entre os dois grupos estudados. O estudo sugere que os acidentes ofídicos causados por serpentes do gênero Bothrops apresentam gravidade semelhante na avaliação admissional e evolução com a mesma proporção de complicações em crianças quando comparados aos acidentes em adultos / Some studies propose that the level of severity of the accidents caused by snakes in children can be associated with a stronger envenoming and a higher risk of later complication if compared to the same accidents in adults. This retrospective study aim to describe the caracteristics of snakebites acidents of the genus Bothrops, and compare their severities, necessity of antivenom, and the risk of developing later complications between children (less than 13 years) and adults, all the accidents where admitted at Hospital Vital Brazil/Instituto Butantan/SP, Brazil (HVB). This retrospective cohort study was carried out by using HVB\'s records of snakebite victims, from December 1999 to June 2003. Patients included were those who brought the snake and/or have the clinical or laboratorial presence of abnormalities compatible with Bothrops envenoming. No statistic differences were found between the two groups of this study concerning the severity of envenoming, number of antivenom vials and the frequency of complications. This study suggests that snakebite accidents are similar between adults and children. Age is not supposed to be a predictor of complication in such accidents

Bacillus subtilis é uma bactéria gram positiva de solo, não patogênica, não colonizadora de tecidos, naturalmente transformável e formadora de esporos utilizada como modelo de estudo de bactérias gram-positivas. Essas características acarretam em vantagens para a produção de proteases de interesse industrial e para utilização como veículo de antígenos vacinais, porém a falta de vetores induzíveis torna sua utilização como ferramenta biológica pouco explorada. No presente trabalho descrevemos a construção de diferentes vetores capazes de expressar os antígenos subunidade B da toxina termo-lábil (LTB) e subunidade estrutural da fímbria CFA/I (CFAB) de Escherichia coli enterotoxigênica (ETEC) e avaliamos seu potencial vacinal. Foi avaliada a imunogenicidade de linhagens capazes de expressar LTB sob o controle de diferentes promotores: PgsiB (induzido em condições de estresse), PlepA (promotor constitutivo) e Pspac (induzido pela adição de IPTG) e em diferentes locais da célula (ancorada à parede celular ou secretada para o meio externo). Avaliamos ainda a imunogenicidade de linhagens capazes de co-expressar LTB e a listeriolisina O (LLO) de Listeria monocytogenes. O antígeno CFAB foi produzido no citoplasma ou ancorado à parede celular de B. subtilis em condições de estresse e as linhagens bacterianas administradas sozinhas ou conjuntamente com a toxina termo-lábil (LT) como adjuvante de mucosa. Camundongos imunizados com células ou esporos de B. subtilis recombinantes desencadearam respostas de anticorpos sistêmicos e secretados específicos para os antígenos (LTB e CFAB), não alterados pela adição do adjuvante. A expressão de LLO causou a supressão da resposta de anticorpos específicos para o antígeno LTB. Os resultados obtidos demonstram a viabilidade do uso de B. subtilis como veículo vacinal. / Bacillus subtilis is a gram positive, generally regarded as safe and spore forming soil bacteria used as a model for genetic and phisiological studies. This safety status allow its use as host for production of industrial protases and its application as vaccine vehicles, however the lack of epissomal inducible expression systems disable the exploration of this organism as a biotechnologic tool. In this work we describe the construction of epissomal vectors able to express the B subunit of the heat-labile toxin (LTB) and the structural subunit of the CFA/I fimbrae (CFAB) from the enterotoxigenic Escherichia coli (ETEC). We evaluate strains able to express LTB under the control of three promoters: PgsiB (stress inducible), PlepA (constitutive) e Pspac (IPTG inducible) and allowing the expression of LTB secreted or anchored to the cell wall We also evaluate the immunogenicity of strains able to co-express LTB and the listeriolysin O (LLO) from Listeria monocytogenes. CFAB was expressed in the cytoplasm or anchored to the cell wall and administred alone or with the mucosal adjuvant LT. Mice immunized both with cells or spores elicited secreted and systemic specific antibodies responses, which were not altered by the addition of the adjuvant LT. LLO expression suppressed the antibodies responses against LTB. The data shows the ability of B. subtilis to be used as vaccine vehicle.

O Vírus Respiratório Sincicial Humano (HRSV) é um dos patógenos mais importantes do trato respiratório. Analisamos as interações das proteínas virais nucleoproteína (N), fosfoproteína (P) e matriz (M) em células HEK-293T. N interage com as proteínas celulares Hsp70, PRMT5 e WDR77; P com Hsp70 e Tropomiosina; e M com Nucleofosmina e Tropomiosina. Cada gene celular foi co-expresso em bactérias com um gene viral possibilitando a co-precipitação das proteínas. Analisamos a interação entre Hsp70 e N ou P, confirmando sua ocorrência em bactérias. Com um conjunto de proteínas mutantes, definimos que as interações são através dos amino terminais de N e P, ou do carboxi terminal de P, e do domínio amino terminal de Hsp70. Superexpressão de Hsp70 por transfecção provocou efeito de estímulo sobre a replicação de HRSV. Imunizações em camundongos com vacinas de DNA para N e P mostraram a indução de resposta celular e humoral. Ensaios de desafio resultaram em redução da carga viral após imunização com N, indicando potencial para sua aplicação em formulação vacinal. / Human respiratory syncytial virus (HRSV) is one of the most important pathogens of the respiratory tract. We analyzed the interactions of viral nucleoprotein (N), phosphoprotein (P) and matrix (M) in HEK-293T. N interacts with the cellular proteins Hsp70, PRMT5 and WDR77; P interacts with Hsp70 and Tropomyosin; and M with Nucleophosmin and Tropomyosin. Each cellular gene was co-expressed with a viral gene in bacteria allowing co-precipitation of proteins. Hsp70 co-expression with N or P proteins confirmed that these interactions also occur in bacteria. Using a set of mutants we found that the N and P amino terminus, P carboxy terminus, and Hsp70 amino terminal domain participate in the interactions. The overexpression of Hsp70 by transfection resulted in stimulation of HRSV replication. Mice immunization with N and P showed that DNA vaccines were capable of inducing humoral and cellular response. In challenge assays it was possible to detect significant virus titer reduction in animals immunized with N, indicating its potential for a vaccine formulation.

Streptococcus mutans é o principal agente etiológico da cárie dental humana, uma doença infecciosa para a qual não há vacina disponível. A influência dos sistemas de transporte ABC na virulência bacteriana suporta seu uso como alvos vacinais. Em S. mutans a proteína ligadora de fosfato (PstS) influencia a expressão de fatores de virulência. A proposta deste trabalho foi caracterizar uma estratégia vacinal de mucosa anti-cárie baseada na proteína PstS como antígeno alvo. Inicialmente, a forma recombinante da proteína foi obtida em E. coli. A caracterização biofísica revelou uma estrutura secundária estável, semelhante a outras proteínas ligadoras e capaz de interagir com seu ligante. Epítopos antigênicos conservados foram identificados na proteína recombinante pela reatividade com soro anti-S. mutans. A proteína rPstS foi imunogênica por via sublingual, combinada ou não à LTK4R e anticorpos rPstS-específicos interferiram na colonização oral in vivo por S. mutans. Os resultados indicam que a proteína rPstS pode ser explorada em estratégias vacinais contra a cárie. / Streptococcus mutans is the main etiological agent of human dental caries, an infectious disease for which there is no vaccine available. The influence of ABC transport systems in bacterial virulence supports its use as vaccine targets. In S. mutans the phosphate binding protein (PstS) influences the expression of virulence traits. The purpose of this work was characterizing an anti-caries mucosal vaccine based on the PstS protein as target antigen. First, a recombinant form of the protein was obtained in E. coli. The biophysical characterization showed a stable secondary structure, similar to other binding proteins and able to interact with its ligand. Conserved antigenic epitopes were identified in the recombinant protein by reactivity with anti- S. mutans serum. The rPstS protein was immunogenic by the sublingual route in combination or not with LTK4R and rPstS-specific antibodies interfered with S. mutans oral colonization in vivo. The results indicated that the recombinant PstS protein can be exploited in vaccine strategies against dental caries.